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Orthotopic Injection of Breast Cancer Cells into the Mammary Fat Pad of Mice to Study Tumor Growth.
Published on: February 8, 2015
Integrated transcriptome interactome study of oncogenes and tumor suppressor genes in breast cancer
G Pranavathiyani1, Raja Rajeswary Thanmalagan1, Naorem Leimarembi Devi1
1Centre for Bioinformatics, School of Life Sciences, Pondicherry University, Pondicherry 605014, India.
Abstract:
Breast cancer is the leading cause for mortality among women worldwide. Dysregulation of oncogenes and tumor suppressor genes is the major reason for the cause of cancer. Understanding these genes will provide clues and insights about their regulatory mechanism and their interplay in cancer. In the present study, an attempt is made to compare the functional characteristics and interactions of oncogenes and tumor suppressor genes to understand their biological role. 431 breast cancer samples from seven publicly available microarray datasets were collected and analysed using GEO2R tool. The identified 416 differentially expressed genes were classified into five gene sets as oncogenes (OG), tumor suppressor genes (TSG), druggable genes, essential genes and other genes. The gene sets were subjected to various analysis such as enrichment analysis (viz., GO, Pathways, Diseases and Drugs), network analysis, calculation of mutation frequencies and Guanine-Cytosine (GC) content. From the results, it was observed that the OG were having high GC content as well as high interactions than TSG. Moreover, the OG are found to have frequent mutations than TSG. The enrichment analysis results suggest that the oncogenes are involved in positive regulation of cellular protein metabolic process, macromolecule biosynthetic process and majorly in cell cycle and focal adhesion pathway in cancer. It was also found that these oncogenes are involved in other diseases such as skin diseases and viral infections. Collagenase, paclitaxel and docetaxel are some of the drugs found to be enriched for oncogenes.
Insights
Oncogenes in breast cancer exhibit higher mutation rates, GC content, and interactions compared to tumor suppressor genes. These findings offer insights into gene regulation and potential therapeutic targets.
Area of Science:
- Genomics
- Molecular Biology
- Oncology
Background:
- Breast cancer is a leading cause of mortality in women globally.
- Gene dysregulation, particularly of oncogenes and tumor suppressor genes, is central to cancer development.
- Understanding gene interplay is crucial for deciphering cancer mechanisms.
Purpose of the Study:
- To compare functional characteristics and interactions of oncogenes (OG) and tumor suppressor genes (TSG) in breast cancer.
- To identify potential regulatory mechanisms and biological roles of these gene types.
- To explore associations with diseases and drug targets.
Main Methods:
- Analysis of 416 differentially expressed genes from 431 breast cancer samples across seven microarray datasets using GEO2R.
- Classification of genes into oncogenes, tumor suppressor genes, druggable, essential, and other gene sets.
- Enrichment analysis (GO, Pathways, Diseases, Drugs), network analysis, mutation frequency, and Guanine-Cytosine (GC) content calculation.
Main Results:
- Oncogenes demonstrated higher GC content and interaction networks compared to tumor suppressor genes.
- Oncogenes exhibited significantly higher mutation frequencies than tumor suppressor genes.
- Enrichment analysis linked oncogenes to cell cycle, focal adhesion pathways, and positive regulation of metabolic/biosynthetic processes.
Conclusions:
- Oncogenes play a significant role in breast cancer progression through increased mutations and pathway involvement.
- Findings suggest oncogenes are implicated in broader diseases like skin conditions and viral infections.
- Identified enriched drugs (collagenase, paclitaxel, docetaxel) offer potential therapeutic avenues targeting oncogenes.
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